Data from a Phase III trial of cabotegravir for HIV prevention has been stopped early because of high efficacy .- Viiv Health Care
ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer Inc. and Shionogi Limited as shareholders announced the interim analysis of the HIV Prevention Trials Network (HPTN) 083 study evaluating the safety and efficacy of investigational, long-acting, injectable cabotegravir for HIV prevention.
In the study cabotegravir was found to be 69% more effective (95% CI 41%-84%) in preventing HIV acquisition in men who have sex with men (MSM) and transgender women who have sex with men when compared to the current standard of care, daily oral emtricitabine/tenofovir disoproxil fumarate 200 mg and 300 mg (FTC/TDF) tablets. The study achieved its primary objective of non-inferiority with the difference approaching superiority in favour of cabotegravir, pending final analysis.
The HPTN 083 study , with approximately 4,600 participants across more than 40 sites in North and South America, Asia, and Africa, is one of the first-ever clinical trials to directly compare two active prevention agents. In a planned interim review, the independent Data and Safety Monitoring Board (DSMB) found the study data clearly indicated that long-acting injectable cabotegravir was highly effective at preventing HIV in the study population. Among the 50 people in the trial who acquired HIV, 12 were randomised to the long-acting cabotegravir arm and 38 were randomised to the daily, oral FTC/TDF arm. This translated to an HIV incidence rate of 0.38% (95% confidence interval [CI] 0.20%- 0.66%) in the cabotegravir group and 1.21% (95% CI 0.86%-1.66%) in the FTC/TDF group.
Adherence to oral FTC/TDF was high, based on a random subset sampling that detected tenofovir (> 0.31 ng/ml) in 87% of all samples tested. Despite this high level of adherence to oral therapy, long-acting cabotegravir was 69% (95% CI 41%-84%) more effective than FTC/TDF in preventing HIV acquisition in the study population.
Safety was similar in the two groups. Most participants in the cabotegravir group (80%) reported pain or tenderness at the injection site, compared to only 31% of those in the FTC/TDF arm, who received placebo injections. Discontinuation due to injection site reactions or injection intolerance in the cabotegravir arm of the study was 2% and there were no discontinuations due to ISRs in the FTC/TDF arm.
Following review of these findings, the DSMB recommended the blinded, randomised portion of the study be stopped early and results released. Participants who were in the FTC/TDF arm will be offered CAB LA and participants in the CAB LA arm will continue to receive it. Participants who do not want to receive CAB LA will be offered FTC/TDF until the end of the originally planned blinded component of the study. The DSMB decision was approved by the U.S. National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), the study sponsor..,
The HPTN 083 study enrolled HIV-negative men who have sex with men and transgender women who have sex with men, participants considered at risk for HIV acquisition. Two-thirds of study participants were under 30 years of age, and 12% were transgender women. Half of the participants in the United States identified as black or African American.
ViiV Healthcare plans to enter talks with the FDA and other agencies to see if the data from a Phase III trial that has just been stopped early because of high efficacy will be enough for a regulatory submission of this long-acting, injectable investigational therapy.